Vasodialation revisited - Need help

After much research and reading of several different threads concerning vasodilation and enhancement in transdermals, I am a confused.

Here is what I understand from my research:

1. Steroids applied topically are vasorestrictive. (unfortunately)

2. When heat (heating pad) is applied to topically applied steroids then the systematic absorption rate is improved nearly 110% by the way of increased blood flow (vasodilatation)

3. Steroids move past the stratum corneum, past the epidermis and eventually into the thick layered dermis.

4. With the application of AAS we are ultimately looking for systematic not localized absorption.

Now, what I am confused on is the “rate limiting step”. I thought that once the steroid gets to the dermis the systematic absorption rate in entirely dependant upon the drug being carried from the dermis into the blood stream (i.e. the rate limiting step).

However, from the responses of Par Deus and Chemo on various forums, I understand that they think the rate limiting step is NOT absorption from the dermis but diffusion through the epidermis or stratum corneum into the dermis. Do steroid freely pass into the blood once they hit the dermis?

Being that steroids are naturally vasorestrictive I would assume absorption from the dermis is slow and indeed hindered by lack of blood flow. Even with the application of ionotophoresis when drugs are practically poured into the skin, systematic absorption is still limited by rate of the dermis.

My point being, if in fact the rate limiting step is the final partitioning from the dermis into the blood stream then topical vasodialators (niacin, capsaicin, ginger, ect.) would prove to be a very worthy and effective addition to a TD formula.

So I ask you, what is the rate limiting step in a transdermal solution? -Your Endo

So, I assume that the rate limiting step primarily depends on the method of administration. Passive transermals seem to be ultimately limiled by the stratum corneum, whereas active or aggressive trandermals which involve the use of ionotophoresis, ultrasound or mechanical penetration seem to be mostly limited by absorption from the dermis. Is this correct?

With that in mind where in relation to the stratum corneum do topical vasodilators take their effect? Do they exert their effects primarily upon the lower layered dermis or do they reach up farther to the stratum corneum and dilate the blood vessels?

If one knew where the actual vasodilation occurred then vasodilators could be applied appropriately to either a passive or active TD system to enhance absorption. What do you think?? -Your Endo